Project Summary Cells are the unit building blocks of tissues and organs, thus, to understand how tissues function, it is important to understand where different types of cells reside in health and disease. In this proposal, we propose to develop a novel spatial genomics platform that will enable multi-modal characterization of tissue structure at the single cell level. This will be revolutionary for the study of tissue organization in development and pathological changes in aging and disease. Our tools will enable us to look at RNA, proteins and regulatory elements in DNA all within the tissue context. We will ensure these novel genomic tools are easy to use and adopt, which will be especially powerful for pathological settings, where tissue resources are precious, and adoption of tools is limited by ease of use. In addition, we are applying this technology to rapidly develop a deep molecular and spatial understanding of COVID19 infection and its impacts in organs throughout the body. The successful completion of this work will lead to a comprehensive toolset for understanding tissue structure from the perspective of single cell organization.